a 4-week, randomized, placebo-controlled, double-blind, efficacy and safety study of hs-25 in adults with primary hypercholesterolemia

Conditions: Primary Hypercholesterolemia

Summary: to determine the efficacy of hs-25 (5, 10, 20 or 30 mg) in reducing low density lipoprotein-cholesterol (ldl-c) levels after a 4-week period of treatment in adults with primary hypercholesterolemia.

this is a 4-week, randomized, double-blind, placebo-controlled study designed to assess the effects of the cholesterol absorption inhibitor hs-25 on ldl-c levels in adults who have untreated ldl-c levels ranging from 130-189 mg/dl and fasting triglyceride levels \< 350 mg/dl. eligibility is restricted to 18-65 year old men or women who are using a highly effective birth control method or are not of childbearing potential. patients with diabetes, a history of myocardial infarction or other clinical evidence of atherosclerotic vascular disease are not eligible for participation in the study.

Eligibility criteria:
inclusion criteria: * men, or women using a highly effective birth control method or not of child-bearing potential, who are 18 to 65 years of age at visit 1 (screening visit). * ldl-c 130 to 189 mg/dl (inclusive) on a cholesterol lowering diet but no lipid modifying drug treatment for at least 6 weeks. a qualifying ldl-c value must be obtained at the beginning and end of the placebo run-in (visit 2 and visit 3) and the visit 3 value must be within 15% of the value at visit 2, higher or lower; the average of both qualifying values must be in the range of 130 to 189 mg/dl (inclusive) for inclusion in the study. * tg ≤ 350 mg/dl on a cholesterol lowering diet but no lipid modifying drug treatment for at least 6 weeks and tg levels must be ≤ 350 mg/dl at both visit 2 and visit 3 * compliance of 80% to 120% with assigned study drug regimen during a 2 week placebo run-in phase. exclusion criteria: * women who are pregnant or breast feeding. * history of stroke, myocardial infarction, unstable angina, heart failure or any arterial revascularization procedure (eg, carotid, coronary, aorta, peripheral arterial). * history of diabetes or glycosylated hemoglobin (hba1c) \> 6.5. * history of moderate to severe lactose intolerance (eg, unable to drink a glass of milk). * history of hospitalization for treatment of a major psychiatric disorder. * history of drug or alcohol abuse as defined by the diagnostic and statistical manual (dsm-5) within the prior 12 months. * history of regular alcohol consumption exceeding 7 drinks/week for females or 14 drinks/week for men (1 drink = 5 ounces of wine or 12 ounces of beer or 1.5 ounces of hard liquor) within 6 months prior to screening. * hospitalization for a duration \> 24 hours for any reason within the prior 3 months that, in the opinion of the investigator, may affect adherence to study procedures. * history of a positive test for human immunodeficiency virus, hepatitis b or hepatitis c. * history of cancer with the exception of well-treated basal cell or squamous cell carcinoma of skin, or in-situ cervical carcinoma. * presence of any condition which, in the opinion of the investigator, is likely to compromise completion of this trial or not be in the best interest of the subject. * history of intolerance to ezetimibe. * participation in a prior study of hs 25. * participation in a study of an investigational drug or device within the prior 3 months unless subject has documentation of placebo administration in a placebo-controlled drug treatment trial only. * treatment with a fibric acid derivative (eg, fenofibrate, gemfibrozil), probucol, warfarin, systemic corticosteroid, cyclosporine or other immunosuppressant agent within the prior 12 weeks. * anticipated need or frequent use of acetaminophen (\> 2 gm/day, that is required \> 4x/week). * vitamins, herbal and dietary supplements must be discontinued at screening unless subject has been on a long-term daily regimen and agrees to continue this regimen during the study. * alanine aminotransferase (alt) \> 1.0 × upper limit of normal (uln) at visit 1, visit 2 or visit 3. * aspartate aminotransferase (ast) \> 1.0 × uln at visit 1, visit 2 or visit 3. * unexplained (not due to exercise or strenuous activity) creatinine kinase increase \> 2 × uln at visit 1, visit 2 or visit 3. * estimated glomerular filtration rate (modification of diet in renal disease) \< 60 ml/min/1.73m2 at visit 1, visit 2 or visit 3. * thyroid stimulating hormone outside of the normal range. * prisoners or subjects who are compulsorily detained (involuntarily incarcerated) for treatment of either a psychiatric or physical disease (eg, infectious disease) must not be enrolled. * any other laboratory abnormality considered by the investigator to be clinically significant. * any subject with an electrocardiogram (ecg) having a qtc interval ≥ 450 msec, or any other abnormality considered by the investigator to be clinically significant at the end of placebo run-in (visit 3) should not be enrolled.

Keywords: hypercholesterolemia cholesterol absorption inhibitor placebo-controlled trial